Sandbox Reserved 705: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
No edit summary
No edit summary
 
(14 intermediate revisions by the same user not shown)
Line 4: Line 4:


''' Human Merlin FERM Domain'''
''' Human Merlin FERM Domain'''
<Structure load='3u8z' size='230' frame='true' align='left' caption='Human Merlin FERM Domain 3u8Z' scene='Insert optional scene name here' />


==Introduction ==
==Introduction ==
Line 60: Line 63:
As showed in the default scene, the structure 3U8Z has in total 4 chains. These are represented by 1 sequence-unique entity. The chains A,B and C possess 9  
As showed in the default scene, the structure 3U8Z has in total 4 chains. These are represented by 1 sequence-unique entity. The chains A,B and C possess 9  
{{Template:ColorKey_Helix}} and 15 {{Template:ColorKey_Strand}} and the chain D has only 9 {{Template:ColorKey_Helix}}and 14  {{Template:ColorKey_Strand}}. You can visualize their <scene name='Sandbox_Reserved_705/Hidoeurf/1'>repartition</scene>.
{{Template:ColorKey_Helix}} and 15 {{Template:ColorKey_Strand}} and the chain D has only 9 {{Template:ColorKey_Helix}}and 14  {{Template:ColorKey_Strand}}. You can visualize their <scene name='Sandbox_Reserved_705/Hidoeurf/1'>repartition</scene>.
===Structural differences===
===Structural differences===
The overall architecture of merlin is similar to that of ERM proteins. Indeed they have almost the same organization : a FERM domain,a central α-helical rod, but lack a C-terminal actin-binding site<ref name= "utile2" />.
The overall architecture of merlin is similar to that of ERM proteins. Indeed they have almost the same organization : a FERM domain,a central α-helical rod, but lack a C-terminal actin-binding site<ref name= "utile2" />.
The closed complex of the Merlin proteins corresponds to the tumor suppressor-active form. As the N-terminus FERM domain and C-terminus are maintained associated, Merlin is in a closed conformation and is able to promote nuclear translocation and inhibt growth<ref>PMID:22482125</ref>.
The closed complex of the Merlin proteins corresponds to the tumor suppressor-active form. As the N-terminus FERM domain and C-terminus are maintained associated, Merlin is in a closed conformation and is able to promote nuclear translocation and inhibt growth<ref>PMID:22482125</ref>.
More precisly,binding of the tail provokes dimerization and unfurling of the F2 motif of the FERM domain.The “closed” complex of merlin-1 is in fact an “open” dimer <ref name="utile" />. Ser-10 and Ser-518 phosphorylation by protein kinase A (PKA) and/or p21-activated kinase(PAK) trigger the "closed" complex <ref>PMID:18071304</ref>. Phosphorylation by PAK and PKA at Ser 518 renders the protein inactive.
More precisly,binding of the tail provokes dimerization and unfurling of the F2 motif of the FERM domain.The “closed” complex of merlin-1 is in fact an “open” dimer <ref name="utile" />.
'''Revoir et compléter la dimérisation'''
===Merlin regulation===
<scene name='Sandbox_Reserved_705/Jofre/1'>Ser-10</scene> and Ser-518 phosphorylation by protein kinase A (PKA) and/or p21-activated kinase(PAK) trigger the "closed" complex <ref>PMID:18071304</ref>. Phosphorylation by PAK and PKA at Ser 518 renders the protein inactive, it reduces the inhibition of cell growth.


===CD44===
Merlin possess a serine 10 that can be phosphorylated by Akt. This phosphorylation directs merlin for proteasome-mediated degradation.<ref>PMID:21750658</ref>. 
CD44 is a cell-surface receptor for hyaluronan (HA a ligand). When HA binds to CD44 the complex promotes tumorigenesis it means it promotes tumor invasion and metastasis. Indeed, CD44 is a receptor presents in the TA3 carcinome mammaire cells and Tr6BC1 schwannoma cells and HA allows their growth.
 
'''Lire ces deux articles pour savoir s'il faut les citer  le 14 c'est de celui ci que j'ai tirer les informations donc je pense que l'on doit le citer<ref>PMID:11316791</ref><ref>PMID:9378774</ref>
===Tumor suppressive function===
 
The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is often involved in tumor proliferation.Indeed overexpression of Akt is often associated with tumor development<ref>PMID:12094235</ref>. Merlin plays a role in controlling the PI3K/Akt pathway by inhibiting Akt signaling <ref>PMID:15598747</ref>.
 
 
CD44 is a cell-surface receptor for hyaluronan (HA a ligand). When HA binds to CD44 the complex promotes tumorigenesis it means it promotes tumor invasion and metastasis.<ref>PMID:11316791</ref> .
'''Lire ces deux articles pour savoir s'il faut les citer  le 14 c'est de celui ci que j'ai tirer les informations donc je pense que l'on doit le citer<ref>PMID:9378774</ref>
<scene name='Sandbox_Reserved_705/Global/4'>charged</scene>
<scene name='Sandbox_Reserved_705/Global/4'>charged</scene>
<scene name='Sandbox_Reserved_705/Sheet/3'>hydrophobic,polar</scene>
<scene name='Sandbox_Reserved_705/Sheet/3'>hydrophobic,polar</scene
{{Template:ColorKey_Hydrophobic}} repartition  {{Template:ColorKey_Polar}} Savoir si on montre les hydrophobes etc et leur intérêt...puisqu'on a leur répartition. Faire un schéma pour la structural difference de merlin et ERM protein pour montrer que c'est plus court. Décrire CD44 role. Qu'ajouter de plus? As tu des idées de schémas que l'on peut faire ou imiter à partir d'une publi ou je sais pas? As tu des idées de structure 3D que l'on peut montrer? Peux tu me dire s'il y a des fautes dans le texte en anglais ( ce qui est le cas je le sais^^) j'ai pas encore tout relu je regardais les deux auttres articles et cherchais les réponses à tes questions ^^'''
===Applications===
Nowadays, late stage melanoma is resistant to any treatment.To achieve better therapies for patients, we need to understand better the signaling pathways of melanoma progression.
Merlin is a target that is seriously considered.
Its levels and activity can be modulated through post-translational modifications<ref>PMID:22912849</ref>.
Phosphorylation at Ser518 of merlin inactivates its growth inhibitive activity. As we explained this phosphorylation can be achieved by cyclic AMP-dependent protein PKA and PAK1.
Phosphorylation of merlin at <scene name='Sandbox_Reserved_705/Resi/1'>Thr-230</scene> and <scene name='Sandbox_Reserved_705/Rez/1'>Ser-315</scene> target the protein for ubiquitination,degradation <ref>PMID:17891137</ref>.This is a mechanism that lowers merlin expression in breast cancer<ref>PMID:21965655</ref>.
However there exist many protein that regulates merlin expression. They may be a useful therapetic target.Therefore scientist need to further inverstigate to determine the pathways that involve the merlin protein.


===Applications===
<ref>PMID:22912849</ref>


== References ==
== References ==
Retrieved from "https://proteopedia.org/Sandbox_Reserved_705"